Tevabon in Moscow
For the use of alendronic acid
Particular attention should be paid to any signs of adverse reactions in the esophagus. The patient should be informed of the need to stop taking the drug and consult a doctor if dysphagia, pain when swallowing, chest pain, or heartburn appears or worsens.
Due to the existing risk of irritation of the mucous membrane of the upper gastrointestinal tract, as well as aggravation of the underlying disease, it is recommended to exercise caution when prescribing the drug to patients with gastrointestinal diseases in the acute phase, such as dysphagia, esophagitis, gastritis, duodenitis, peptic ulcer of the stomach and duodenum, and also recently suffered (within the previous year) diseases of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, active bleeding from the gastrointestinal tract, surgical intervention in the upper gastrointestinal tract, except pyloroplasty).
Cases of osteonecrosis of the jaw, usually associated with tooth extraction and/or local infection (including osteomyelitis), have been reported in patients with cancer receiving treatment regimens that include BP (primarily IV). Many of these patients also received chemotherapy and corticosteroids. There have also been reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral BF. Before using BF, patients with associated risk factors (for example, cancer, chemotherapy, radiation therapy, corticosteroid therapy, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment. Patients being treated for FD should avoid invasive dental procedures whenever possible. In patients with osteonecrosis of the jaw who are on FD therapy, dental surgery may lead to a worsening of the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of BF. Prescriptions and recommendations of the attending physician should be based on an individual assessment of the benefit/risk ratio for each patient.
The time for the onset of pain in bones, joints and muscles in patients during BF therapy varies from 1 day to several months after the start of treatment. In most patients, after stopping treatment, there was a decrease in the severity of pain; in some patients, pain reappeared when therapy was resumed with the same or another BP.
If the patient forgot to take an alendronic acid tablet, it should be taken the next morning. You should not take two tablets in one day, you must continue to take 1 tablet. 1 time per week on the day that was chosen for administration from the very beginning of treatment.
In patients with hypocalcemia, hypovitaminosis D and hypoparathyroidism, it is necessary to carry out corrective therapy for disorders of mineral metabolism before starting treatment with alendronic acid. Due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in serum calcium and phosphorus concentrations may be observed during treatment. There are isolated reports of symptomatic hypocalcemia, sometimes severe, usually in patients with a predisposition to it (for example, hypoparathyroidism, vitamin D deficiency, calcium malabsorption).
There are reports of stress fractures of the proximal femur during long-term treatment with alendronic acid (from 18 months to 10 years). Fractures occurred after minimal or no trauma. Some patients first develop pain in the proximal femur and persist for weeks or even months before culminating in a femoral fracture. Often the fractures were bilateral, so if one femur is fractured in a patient, it is necessary to monitor the condition of the other femur.
In patients taking alendronic acid, especially with concomitant therapy with corticosteroids, it is extremely important to ensure sufficient intake of calcium and vitamin D from food or in the form of medications.
Absorption of BF is significantly reduced by simultaneous food intake.
For the use of alfacalcidol
Alfacalcidol may increase hypercalcemia and/or hypercalciuria when administered to patients with a disease associated with uncontrolled hyperproduction of calcitriol (for example, leukemia, lymphoma, sarcoidosis), and may also increase hyperphosphatemia. If the plasma calcium concentration is more than 2.6 mmol/l, it is necessary to avoid taking other calcium-containing drugs. If there is no effect, you should stop taking alfacalcidol capsules until the serum calcium concentration normalizes (2.2–2.6 mmol/l). The concentration of calcium and phosphates in the blood is monitored before treatment with alfacalcidol and, if necessary, corrective therapy is carried out. When treating with alfacalcidol, the concentration of electrolytes is determined at the beginning once a week, when the maximum concentration is reached and throughout the entire period of treatment - every 3-5 weeks, and the activity of alkaline phosphatase is monitored (in case of impaired renal function (creatinine Cl more than 35 ml/min) - weekly control).
Peanut butter can cause severe allergic reactions in rare cases.
Patients with hereditary fructose intolerance or fructose malabsorption should not be prescribed Tevabon as the kit contains alfacalcidol capsules containing sorbitol.
Impact on the ability to drive a car and operate machinery
Due to the possibility of developing side effects from the central nervous system during the treatment period, care must be taken when driving vehicles, as well as other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Tevabon instructions for use
Active ingredient : Alendronic acid + Alfacalcidol ATX M05BB03 Alendronic acid + Colecalciferol
Pharmacological group Correctors of bone and cartilage tissue metabolism in combinations
Nosological classification (ICD-10) M81.0 Postmenopausal osteoporosis M81.4 Drug-induced osteoporosis
Composition and release form Tablets and capsules set 1 set of tablets 1 tablet active substance: alendronic acid 70 mg (in the form of sodium alendronate monohydrate 81.2 mg) excipients: croscarmellose sodium - 3 mg; magnesium stearate - 2 mg; MCC - 113.8 mg capsules 1 caps. active substance: alfacalcidol 1 mcg excipients: alpha-tocopherol - 0.02 mg; peanut oil - 98.8 mg; citric acid - 0.015 mg; propyl gallate - 0.02 mg; ethanol - 1.144 mg
shell: anidrisorb 85/70 (sorbitol - 25-40%, sorbitan - 20-30%, mannitol - 0-6%, higher polyols - 12.5-19%, water - 15-17%) - 7.88 mg ; glycerol 85% - 11.78 mg; gelatin - 48.27 mg; titanium dioxide E171 - 0.68 mg; black ink A10379 (shellac, black iron oxide dye, denatured ethanol (methylated alcohol), isopropanol, 1-butanol, ethyl acetate) 1 tablet each and 7 capsules in aluminum foil blisters; 1 blister with a tablet and 1 blister with capsules in a cardboard envelope; There are 4 or 12 envelopes in a cardboard pack.
Description of the dosage form Tablets: white or almost white, round, flat, chamfered, with an engraving “T” on one side. Capsules: white or off-white oval opaque soft gelatin containing a pale yellow oil solution, marked “1.0” in black ink.
Pharmacological action Pharmacological action - inhibiting bone resorption, regulating calcium-phosphorus metabolism.
Pharmacokinetics Alendronic acid Absorption. When taken orally on an empty stomach in a dose range from 5 to 70 mg immediately 2 hours before breakfast, the bioavailability of alendronic acid in women is 0.64%, in men - 0.6%. The bioavailability of alendronic acid is reduced by 40% when taken on an empty stomach 1–1.5 hours before breakfast. After drinking coffee and orange juice, bioavailability is reduced by approximately 60%. The concentration of alendronic acid in the blood plasma after oral administration at a therapeutic dose is below the possible limit of detection (less than 5 ng/ml). Distribution. The binding of alendronic acid to plasma proteins is about 78%. Alendronic acid is distributed in soft tissues, and then quickly redistributed to the bones, where it is fixed, or is excreted through the kidneys. Metabolism. Does not undergo biotransformation. Excretion. Output unchanged. The elimination process is characterized by a rapid decrease in the concentration of alendronic acid in the blood plasma and an extremely slow release from the bones. Alfacalcidol Absorption. After oral administration, alfacalcidol is rapidly absorbed from the gastrointestinal tract. The maximum concentration is reached 8–12 hours after a single dose of alfacalcidol. Bioavailability when taken orally is about 100%. Metabolism. The pharmacological effects of alfacalcidol are realized after its conversion in the body to calcitriol. The conversion of alfacalcidol to calcitriol occurs in the liver by hydroxylation at the 25th carbon atom, and the hydroxylation process occurs very quickly (it is substrate-dependent) and does not depend on the functional state of the liver. The maximum concentration of calcitriol in the body is reached 8–12 hours after a single dose of alfacalcidol. Unlike native vitamin D, alfacalcidol does not require hydroxylation in the kidneys, therefore it is effective even in patients with reduced activity of renal 1-alpha-hydroxylase (kidney pathology, old age). Excretion. Calcitriol is excreted by the kidneys and liver in approximately equal parts, T1/2 is about 35 hours.
Pharmacodynamics Alendronic acid, being a bisphosphonate (BP), inhibits the process of active bone tissue resorption caused by osteoclasts without directly affecting the formation of new bone tissue. Having a tropism for bone hydroxyapatite, alendronic acid accumulates mainly in zones of its active resorption. The mechanism of action is associated with suppression of functional activity and stimulation of osteoclast apoptosis. During therapy with alendronic acid, bone mineralization increases and its quality characteristics improve. Alfacalcidol is a regulator of calcium-phosphorus metabolism, a precursor of the active metabolite of vitamin D3 - calcitriol. Increases the absorption of calcium and phosphorus in the intestines, increases their reabsorption in the kidneys, restores a positive calcium balance in the treatment of calcium malabsorption syndrome, reduces the concentration of parathyroid hormone in the blood. By influencing both parts of the bone remodeling process (resorption and synthesis), alfacalcidol not only increases the mineralization of bone tissue, but increases its elasticity by stimulating the synthesis of bone matrix proteins, bone morphogenetic proteins, and bone growth factors. When treated with alfacalcidol, bone with a normal histological structure is formed, the strength of bone tissue increases in all parts of the skeleton. Alendronic acid and alfacalcidol increase bone strength, and their effects are synergistic due to different mechanisms of action. The inhibition of catabolic processes in bones by alendronic acid is complemented by the bone anabolic effect of alfacalcidol, which leads to the formation of normal bone structure. Due to the pharmacological effects of both substances, their use in combination reduces the potential risk of developing hypocalcemia, hypercalcemia and hypercalciuria. A significant reduction in the risk of fractures is achieved not only by increasing bone strength, but also due to the extraosseous (pleiotropic) effect of alfacalcidol - increasing muscle strength, accelerating the speed of muscle reaction.
Indications for the drug Tevabon : postmenopausal osteoporosis; osteoporosis caused by the use of glucocorticosteroid drugs.
Contraindications: hypersensitivity to alendronic acid, alfacalcidol and other components of the drug; conditions leading to slower movement of food through the esophagus (including strictures or achalasia of the esophagus); the patient's inability to stand or sit upright for at least 30 minutes; hypocalcemia; hypercalcemia; Burnett's syndrome and/or milk-alkali syndrome (plasma calcium concentrations more than 2.6 mmol/l, calcium phosphate more than 3.7 mmol/l, pH more than 7.44); severe renal dysfunction (creatinine Cl less than 35 ml/min); patients on hemodialysis; hypervitaminosis D; hyperphosphatemia (except for hyperphosphatemia in hypoparathyroidism); hypermagnesemia; sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption; childhood; period of pregnancy and breastfeeding. With caution: gastrointestinal diseases in the acute phase, incl. dysphagia, esophagitis, gastritis, duodenitis, peptic ulcer of the stomach and duodenum; hypoparathyroidism, hypovitaminosis D, calcium malabsorption, nephrolithiasis, atherosclerosis, renal dysfunction (creatinine Cl more than 35 ml/min), chronic heart failure, in patients with an increased risk of developing hypercalcemia, incl. for leukemia, lymphoma, sarcoidosis, pulmonary tuberculosis (active form).
Use during pregnancy and breastfeeding Due to insufficient data on the use of alendronic acid and/or the risk of overdose of alfacalcidol, Tevabon is contraindicated during pregnancy and breastfeeding.
Side effects of the drug Tevabon Side effects are classified according to the following frequency: very often - at least 10%; often - at least 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases. When using alendronic acid From the digestive system: often - abdominal pain, dyspepsia, sour belching, diarrhea, dysphagia, flatulence, gastritis, stomach ulcer, ulceration of the esophageal mucosa; uncommon - nausea, vomiting, constipation, gastritis, esophagitis, erosion of the esophageal mucosa, melena; rarely - stricture of the esophagus, ulceration of the mucous membrane of the oropharynx, perforation of the esophagus, bleeding from the upper gastrointestinal tract (the connection with the use of alendronic acid has not been established). From the musculoskeletal system: often - pain in bones, muscles, joints, muscle cramps; rarely - osteonecrosis of the jaw, mainly in cancer patients taking BF, but similar cases were also observed in patients undergoing therapy for osteoporosis; unknown frequency - stress fracture of the proximal femur, associated or not associated with trauma. Metabolic: rarely - symptomatic hypocalcemia, usually associated with predisposing conditions, hypophosphatemia. From the side of the central nervous system: often - headache. From the senses: rarely - uveitis, scleritis, episcleritis. Allergic reactions: infrequently - rash, itching, erythema; rarely - rash associated with photosensitivity, urticaria, angioedema; very rarely - severe skin reactions, including erythema multiforme exudative (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome). Other: rarely - transient symptoms similar to those in the acute phase of the disease (myalgia, malaise and fever), usually at the beginning of treatment. When using alfacalcidol Metabolic disorders: rarely - hypercalcemia; very rarely - a slight increase in the concentration of HDL in the blood plasma. In patients with severe renal impairment, hyperphosphatemia and heterotopic calcifications in the cornea and blood vessels may develop. From the digestive system: uncommon - anorexia, vomiting, heartburn, abdominal pain, nausea, dry mouth, discomfort in the epigastric region, constipation, diarrhea; rarely - a slight increase in the activity of liver enzymes in plasma (ALT, AST). From the side of the central nervous system: rarely - weakness, fatigue, dizziness, drowsiness. From the cardiovascular system: rarely - tachycardia. From the musculoskeletal system: infrequently - moderate pain in muscles, bones, joints. Allergic reactions: rarely - skin rash, itching; very rarely - anaphylactic shock associated with peanut butter. Due to the multidirectional effects of alendronic acid and alfacalcidol on the concentration of calcium in the blood serum, the use of a combination of these drugs allows one to avoid sharp fluctuations in the concentration of calcium in the serum.
Interaction When taken simultaneously with food, drinks containing calcium (including mineral water), nutritional supplements, antacids and other oral medications, the absorption of alendronic acid may be impaired. In this regard, the interval between taking alendronic acid and other oral medications should be at least 30 minutes. The combined use of alendronic acid (but not simultaneous use) with estrogen preparations is not accompanied by a change in their action or the development of side effects. Oral administration of prednisolone is not accompanied by clinically significant changes in the bioavailability of alendronic acid. GCS enhance the side effects of alendronic acid on the gastrointestinal tract. With simultaneous use of alfacalcidol with cardiac glycosides, the risk of arrhythmia increases. Inducers of microsomal liver enzymes (including phenytoin and phenobarbital) reduce, and inhibitors increase, the concentration of alfacalcidol in plasma (a change in its effectiveness is possible). The absorption of alfacalcidol is reduced when it is used together with mineral oil (for a long time), cholestyramine, colestipol, sucralfate, antacids, and albumin-based drugs. In this regard, you should not take alfacalcidol capsules simultaneously with antacids containing aluminum; the interval between taking these drugs should be at least 2 hours. Taking antacids increases the risk of developing hypermagnesemia and hyperaluminemia. The toxic effect is weakened by retinol, tocopherol, ascorbic acid, pantothenic acid, thiamine, riboflavin. In perimenopausal women, the effect of alfacalcidol may be enhanced by estrogens. Calcitonin, derivatives of etidronic and pamidronic acids, plicamycin and GCS reduce the effect of alfacalcidol. Alfacalcidol increases the absorption of phosphorus-containing drugs and the risk of hyperphosphatemia. The simultaneous use of alfacalcidol with calcium preparations and thiazide diuretics can cause hypercalcemia by increasing the absorption of calcium in the intestine and increasing its reabsorption in the kidneys. During therapy with alfacalcidol, other preparations of vitamin D and its derivatives should not be prescribed due to possible additive interactions and an increased risk of hypercalcemia.
Overdose of Alendronic acid Symptoms: possible hypocalcemia, hypophosphatemia, diarrhea, heartburn, esophagitis, erosive and ulcerative lesions of the gastrointestinal mucosa. Treatment: taking milk or an antacid to bind alendronic acid. Due to the risk of esophageal irritation, vomiting should not be induced. The patient should be in an upright position. Alfacalcidol Early symptoms of hypervitaminosis D (due to hypercalcemia): diarrhea, constipation, nausea, vomiting, dry mouth, anorexia, metallic taste in the mouth, hypercalciuria, polyuria, polydipsia, pollakiuria/nocturia, headache, fatigue, general weakness, myalgia, pain in the bones. Late symptoms of hypervitaminosis D: dizziness, confusion, drowsiness, heart rhythm disturbances, skin itching, increased blood pressure, conjunctival hyperemia, nephrolithiasis, weight loss, photophobia, pancreatitis, gastralgia; rarely - changes in psyche and mood. Symptoms of chronic vitamin D intoxication: calcification of soft tissues, blood vessels and internal organs (kidneys, lungs), renal failure, cardiovascular failure, growth impairment in children. Treatment: discontinue the drug. In the early stages of acute overdose, the administration of mineral oil may have a positive effect (which helps to reduce absorption and increase excretion of alfacalcidol in feces). In severe cases, hydration is carried out with the introduction of infusion saline solutions, loop diuretics, corticosteroids, bisphosphonates, calcitonin are prescribed, and hemodialysis is carried out using solutions with low calcium content. Blood electrolytes, renal and cardiac function (as measured by ECG) should be monitored, especially in patients receiving digoxin. There is no specific antidote.
Method of administration and dosage The drug Tevabon consists of two dosage forms: alendronic acid tablets and alfacalcidol capsules. To ensure normal absorption and reduce the risk of adverse reactions, the recommendations for use and dosage should be strictly followed. Alendronic acid Orally, 1 tablet. (70 mg) 1 time per week with a glass of water, at least 30 minutes before the first meal, drinks or other drugs. Take only plain water, since other drinks (including mineral water), foods and some drugs can reduce the bioavailability of alendronic acid. The tablets must not be chewed or dissolved. After taking the tablet, the patient must maintain an upright position (standing or sitting) for at least 30 minutes. Do not take the tablet before bed or before getting out of bed in the morning. Elderly patients. No dose adjustment is required. Kidney failure. When creatinine Cl is more than 35 ml/min, no dose adjustment is required. Alfacalcidol 1 capsule orally. (1 mcg) 1 time per day in the evening every day. Capsules should be swallowed whole with sufficient liquid. The drug Tevabon is intended for long-term use.
Special instructions For the use of alendronic acid, special attention should be paid to any signs of adverse reactions in the esophagus. The patient should be informed of the need to stop taking the drug and consult a doctor if dysphagia, pain when swallowing, chest pain, or heartburn appears or worsens. Due to the existing risk of irritation of the mucous membrane of the upper gastrointestinal tract, as well as aggravation of the underlying disease, it is recommended to exercise caution when prescribing the drug to patients with gastrointestinal diseases in the acute phase, such as dysphagia, esophagitis, gastritis, duodenitis, peptic ulcer of the stomach and duodenum, and also recently suffered (within the previous year) diseases of the gastrointestinal tract (peptic ulcer of the stomach and duodenum, active bleeding from the gastrointestinal tract, surgical intervention in the upper gastrointestinal tract, except pyloroplasty). Cases of osteonecrosis of the jaw, usually associated with tooth extraction and/or local infection (including osteomyelitis), have been reported in patients with cancer receiving treatment regimens that include BP (primarily IV). Many of these patients also received chemotherapy and corticosteroids. There have also been reports of osteonecrosis of the jaw in patients with osteoporosis receiving oral BF. Before using BF, patients with associated risk factors (for example, cancer, chemotherapy, radiation therapy, corticosteroid therapy, poor oral hygiene) should undergo a dental examination with appropriate preventive dental treatment. Patients being treated for FD should avoid invasive dental procedures whenever possible. In patients with osteonecrosis of the jaw who are on FD therapy, dental surgery may lead to a worsening of the condition. If surgical interventions are necessary, it should be taken into account that there is no data on the possibility of reducing the risk of developing osteonecrosis of the jaw after discontinuation of BF. Prescriptions and recommendations of the attending physician should be based on an individual assessment of the benefit/risk ratio for each patient. The time for the onset of pain in bones, joints and muscles in patients during BF therapy varies from 1 day to several months after the start of treatment. In most patients, after stopping treatment, there was a decrease in the severity of pain; in some patients, pain reappeared when therapy was resumed with the same or another BP. If the patient forgot to take an alendronic acid tablet, it should be taken the next morning. You should not take two tablets in one day, you must continue to take 1 tablet. 1 time per week on the day that was chosen for administration from the very beginning of treatment. In patients with hypocalcemia, hypovitaminosis D and hypoparathyroidism, it is necessary to carry out corrective therapy for disorders of mineral metabolism before starting treatment with alendronic acid. Due to the positive effect of alendronic acid on bone mineral density, a slight asymptomatic decrease in serum calcium and phosphorus concentrations may be observed during treatment. There are isolated reports of symptomatic hypocalcemia, sometimes severe, usually in patients with a predisposition to it (for example, hypoparathyroidism, vitamin D deficiency, calcium malabsorption). There are reports of stress fractures of the proximal femur during long-term treatment with alendronic acid (from 18 months to 10 years). Fractures occurred after minimal or no trauma. Some patients first develop pain in the proximal femur and persist for weeks or even months before culminating in a femoral fracture. Often the fractures were bilateral, so if one femur is fractured in a patient, it is necessary to monitor the condition of the other femur. In patients taking alendronic acid, especially with concomitant therapy with corticosteroids, it is extremely important to ensure sufficient intake of calcium and vitamin D from food or in the form of medications. Absorption of BF is significantly reduced by simultaneous food intake. For the use of alfacalcidol, alfacalcidol may increase hypercalcemia and/or hypercalciuria when administered to patients with a disease associated with uncontrolled hyperproduction of calcitriol (for example, leukemia, lymphoma, sarcoidosis), and may also increase hyperphosphatemia. If the plasma calcium concentration is more than 2.6 mmol/l, it is necessary to avoid taking other calcium-containing drugs. If there is no effect, you should stop taking alfacalcidol capsules until the serum calcium concentration normalizes (2.2–2.6 mmol/l). The concentration of calcium and phosphates in the blood is monitored before treatment with alfacalcidol and, if necessary, corrective therapy is carried out. When treating with alfacalcidol, the concentration of electrolytes is determined at the beginning once a week, when the maximum concentration is reached and throughout the entire period of treatment - every 3-5 weeks, and the activity of alkaline phosphatase is monitored (in case of impaired renal function (creatinine Cl more than 35 ml/min) - weekly control). Peanut butter can cause severe allergic reactions in rare cases. Patients with hereditary fructose intolerance or fructose malabsorption should not be prescribed Tevabon as the kit contains alfacalcidol capsules containing sorbitol.
Effect on the ability to drive a car and operate machinery Due to the possibility of developing side effects from the central nervous system during the treatment period, care must be taken when driving vehicles, as well as other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Conditions for dispensing from pharmacies By prescription.
Storage conditions for the drug Tevabon At a temperature not exceeding 25 °C.
The shelf life of Tevabon Tablets is 2.5 years; capsules - 3 years.
